Abstract
Factor Xa (fXa) is a critical serine protease situated at the confluence of the intrinsic and extrinsic pathways of the blood coagulation cascade. FXa catalyses the conversion of prothrombin to thrombin via the prothrombinase complex. Its singular role in thrombin generation, coupled with its potentiating effects on clot formation render it an attractive target for therapeutic intervention. Otamixaban is a synthetically derived parenteral fXa inhibitor currently in late stage clinical development at Sanofi-Aventis for the management of acute coronary syndrome. Otamixaban is a potent (Ki = 0.5 nM), selective, rapid acting, competitive and reversible fXa inhibitor that effectively inhibits both free and prothrombinase-bound fXa. In vivo experiments have demonstrated that Otamixaban is highly efficacious in rodent, canine and porcine models of thrombosis. In addition, recent clinical findings indicate that Otamixaban is efficacious, safe and well tolerated in humans and therefore has considerable potential for the treatment of acute coronary syndrome. This review article chronicles the discovery and pre-clinical data surrounding the fXa inhibitor Otamixaban as well as the recent clinical findings in humans.
Keywords: venous thromboembolism, anticoagulant, carotid artery blood flow, RPR109891, prothrombin time
Current Medicinal Chemistry
Title: The Discovery of the Factor Xa Inhibitor Otamixaban: From Lead Identification to Clinical Development
Volume: 14 Issue: 23
Author(s): Kevin R. Guertin and Yong-Mi Choi
Affiliation:
Keywords: venous thromboembolism, anticoagulant, carotid artery blood flow, RPR109891, prothrombin time
Abstract: Factor Xa (fXa) is a critical serine protease situated at the confluence of the intrinsic and extrinsic pathways of the blood coagulation cascade. FXa catalyses the conversion of prothrombin to thrombin via the prothrombinase complex. Its singular role in thrombin generation, coupled with its potentiating effects on clot formation render it an attractive target for therapeutic intervention. Otamixaban is a synthetically derived parenteral fXa inhibitor currently in late stage clinical development at Sanofi-Aventis for the management of acute coronary syndrome. Otamixaban is a potent (Ki = 0.5 nM), selective, rapid acting, competitive and reversible fXa inhibitor that effectively inhibits both free and prothrombinase-bound fXa. In vivo experiments have demonstrated that Otamixaban is highly efficacious in rodent, canine and porcine models of thrombosis. In addition, recent clinical findings indicate that Otamixaban is efficacious, safe and well tolerated in humans and therefore has considerable potential for the treatment of acute coronary syndrome. This review article chronicles the discovery and pre-clinical data surrounding the fXa inhibitor Otamixaban as well as the recent clinical findings in humans.
Export Options
About this article
Cite this article as:
Guertin R. Kevin and Choi Yong-Mi, The Discovery of the Factor Xa Inhibitor Otamixaban: From Lead Identification to Clinical Development, Current Medicinal Chemistry 2007; 14 (23) . https://dx.doi.org/10.2174/092986707782023659
DOI https://dx.doi.org/10.2174/092986707782023659 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the Treatment of Chronic Inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Recent Advances in the Treatment of Neurogenic Erectile Dysfunction
Recent Patents on CNS Drug Discovery (Discontinued) Regulation of Glycolytic and Mitochondrial Metabolism by Ras
Current Pharmaceutical Biotechnology Coronary Intravascular Ultrasound (IVUS): Contemporary Applications and Bases for the Future
Recent Patents on Medical Imaging Green Tea, A Medicinal Food with Promising Neurological Benefits
Current Neuropharmacology Targeted Tumor Diagnosis and Therapy with Peptide Hormones as Radiopharmaceuticals
Anti-Cancer Agents in Medicinal Chemistry New Actors for the Immunological Mechanisms Involved in the Materno- Fetal Tolerance
Current Women`s Health Reviews Nanotechnology as an Adjunct Tool for Transplanting Engineered Cells and Tissues
Current Molecular Medicine The Etiology of Hypertension in the Metabolic Syndrome Part Three: The Regulation and Dysregulation of Blood Pressure
Current Vascular Pharmacology Exploring Novel Target Space: A Need to Partner High Throughput Docking and Ligand-Based Similarity Searches?
Combinatorial Chemistry & High Throughput Screening Solution NMR Study of the Transmembrane Domain of Single-Span Membrane Proteins: Opportunities and Strategies
Current Protein & Peptide Science Sensitive Sensors Based on Phosphorus Dendrimers
Current Organic Chemistry Prevention of Macrovascular Disease in Type 2 Diabetic Patients: Blockade of the Renin-Angiotensin-Aldosterone System
Current Diabetes Reviews Recent Progress in the Design of Selectin Inhibitors
Mini-Reviews in Medicinal Chemistry Strategies for Leukotriene Modulation in Dermatology: Even More Visionary Perspectives? An Update
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry The Smart Targeting of Nanoparticles
Current Pharmaceutical Design Challenges and Controversies in Autoantibodies Associated with Systemic Rheumatic Diseases
Current Rheumatology Reviews Molecular Mechanisms and Therapeutic Application of NSAIDs and Derived Compounds in Alzheimers Disease
Current Alzheimer Research 3D-QSAR Studies of Various Diaryl Urea Derivatives of Multi-targeted Receptor Tyrosine Kinase Inhibitors: Molecular Field Analysis Approach
Letters in Drug Design & Discovery Heptahelical and Other G-Protein-Coupled Receptors (GPCRs) Signaling
Current Medicinal Chemistry Targeting Leukotrienes for the Treatment of COPD?
Inflammation & Allergy - Drug Targets (Discontinued)